title: Operational tolerance in nonvascularized transplant models induced by AR-C117977, a monocarboxylate transporter inhibitor.
abstract: AR-C117977, a monocarboxylate transporter inhibitor, reduces immune responses both in vitro and in vivo, maintains long-term graft survival, and induces operational tolerance. To evaluate the immunosuppressive limitations of AR-C117977, this study was performed in nonvascularized transplant models noted for their refractive response to standard immunosuppressive agents. Rat skin was transplanted from DA(RT1avl) into PVG(RT1c) and the reverse. Mouse islet allotransplantation was performed with BALB/c H2d donors and C57Bl/6J H2b recipients. In the skin graft model, AR-C117977 monotherapy was associated with long-term skin graft survival in one rat strain combination. AR-C117977 and cyclosporine A (CsA) in combination resulted in significant prolongation of graft survival in both rat strains. CsA monotherapy did not prevent acute rejection in either strain. Islet allograft survival was moderately prolonged with CsA or AR-C117977. AR-C117977 is an efficient immunosuppressive drug in stringent rodent transplant models and further studies are warranted.
authors.affiliation: Department of Nephrology and Transplantation, University Hospital, Malmo, Sweden. clara.pahlman@med.lu.se
authors.forename: Clara
authors.initials: C
authors.lastname: Påhlman
authors.forename: Helene
authors.initials: H
authors.lastname: Malm
authors.forename: Zhongquan
authors.initials: Z
authors.lastname: Qi
authors.forename: Béla
authors.initials: B
authors.lastname: Veress
authors.forename: Douglas
authors.initials: D
authors.lastname: Ferguson
authors.forename: Robert
authors.initials: R
authors.lastname: Bundick
authors.forename: Clare
authors.initials: C
authors.lastname: Murray
authors.forename: David
authors.initials: D
authors.lastname: Donald
authors.forename: Henrik
authors.initials: H
authors.lastname: Ekberg
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D007108:Immune Tolerance / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D027501:Monocarboxylic Acid Transporters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D016038:Skin Transplantation; D027981:Symporters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors; D014184:Transplantation, Homologous; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D016572:Cyclosporine; D006571:Heterocyclic Compounds; D007166:Immunosuppressive Agents; D027501:Monocarboxylic Acid Transporters; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C525748:AR C117977